Patients with a baseline TMTV >510 cm3 had a 5-year progression-free survival of 33% compared with 65% for patients with lower TMTV values. TMTV >510 cm3 also was associated with significantly worse overall survival at 5 years.

A multivariable analysis identified TMTV and Follicular Lymphoma International Prognostic Index-2 (FLIPI2) as independent predictors of 5-year PFS. Combining TMTV and FLIPI2 allowed patient stratification into poor-, intermediate-, and favorable-risk groups, as reported online in the Journal of Clinical Oncology.

"In this study, baseline TMTV was the most robust pretreatment predictor of outcome in high-tumor-burden follicular lymphoma," Michel Meignan, MD, PhD, of Hôpital Henri Mondor in Créteil, France, and co-authors concluded. "Patients with a high TMTV >510 cm3 had a markedly inferior 5-year PFS with a median PFS of less than 3 years and an increased risk of death. Conversely, a metabolic volume below this cutoff in the remaining 70% of patients predicted a median PFS beyond 6 years. Importantly, TMTV was a strong predictor of early progression within the first 1 to 2 years after beginning therapy."

The novel aspect of the study was the use of pretreatment PET-derived tumor metabolism data to predict subsequent outcome in advanced or high tumor burden follicular lymphoma, said Brad Kahl, MD, of Washington University in St. Louis.

"We're constantly trying to figure out who are the truly high-risk follicular lymphoma patients at diagnosis or at least early in the course of treatment. Right now, the only way we can identify those patients is to look at the length of their first remission, so you can't figure out who's in the good group and who's in the bad group until a couple of years have elapsed."

"This particular dataset may provide us another tool that helps us figure out who these patients are at diagnosis. We're not there yet, but this could be a tool that helps us get there."

Treatment advances have resulted in prolonged remissions for most patients with follicular lymphoma. Nonetheless, 20% of patients treated with immunotherapy have disease progression within 2 years, and half of the patients die within 5 years, the authors noted in their background information.

Identifying high-risk, poor-prognosis patients prior to initiation of treatment has proved challenging by means of conventional methods, including FLIPI, FLIPI2, and conventional CT. In a previous study, Meignan and colleagues showed that a post-treatment positive FDG-PET or CT-PET scan was associated with an increased risk of disease progression and death. Post-induction PET status had substantially greater predictive value than FLIPI/FLIPI2 or CT findings.

Recent studies generated support for baseline TMTV assessment in Hodgkin lymphoma, diffuse large B-cell lymphoma, and peripheral T-cell lymphoma. Meignan and colleagues continued the evaluation of TMTV in 185 patients with high tumor burden or advanced-stage follicular lymphoma, recruited into three prospective clinical trials of immunotherapy.

Baseline TMTV was determined by central review of FDG-PET-CT scans. Reviewers calculated TMTV by adding the metabolic volumes of all local nodal and extranodal lesions.

The patients had a median age of 55 and a median follow-up of 64 months. More than 90% of the patients had stage III-IV disease, 37% had a FLIPI score of 3 to 5, and 31% had a FLIP2 score of 3 to 5.

The data showed that a 29% of patients had a baseline TMTV >510 cm3, which was associated with almost a threefold increase in the 5-year hazard for progression or death (HR 2.90, P<0.001). The 5-year overall survival was 85% among patients with a baseline TMTV >510 cm3, compared with 95% for patients with lower TMTV values (HR 3.45, P=0.010).

By multivariate analysis, both baseline TMTV and FLIPI2 score were independent predictors of PFS (HR 2.3, P=0.002; HR 2.2, P=0.002, respectively). The combination of TMTV and FLIPI2 score resulted in three distinct risk groups with respect to 5-year PFS:

Low TMTV + low FLIPI2 score - 69% (reference)

High TMTV + intermediate to high risk FLIPI2 - 20%, HR 5.0, P<0.001

High TMTV or intermediate-to-high-risk FLIPI2 - 46%, HR 2.1, P=0.007

"The strong independent predictive value of baseline TMTV complements our previous analysis, which identified the powerful prognostic impact of a post-induction PET scan after first-line therapy," the authors concluded. "This analysis demonstrates that a high-risk population can also be identified at staging by combining quantitative PET with conventional prognostic indices."

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